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Caveolin modulates integrin function and mechanical activation in the cardiomyocyte
Author(s) -
IsraeliRosenberg Sharon,
Chen Chao,
Li Ruixia,
Deussen Daniel N.,
Niesman Ingrid R.,
Okada Hideshi,
Pately Hemal H.,
Roth David M.,
Ross Robert S.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-243139
Subject(s) - mechanotransduction , integrin , caveolin 3 , myocyte , caveolae , microbiology and biotechnology , biology , colocalization , signal transduction , receptor , biochemistry
ABSTRACT β1 integrins (β1) transduce mechanical signals in many cells, including cardiac myocytes (CM). Given their close localization, as well as their role in mechanotransduction and signaling, we hypothesized that caveolin (Cav) proteins might regulate integrins in the CM. β1 localization, complex formation, activation state, and signaling were analyzed using wild‐type, Cav3 knockout, and Cav3 CM‐specific transgenic heart and myocyte samples. Studies were performed under basal and mechanically loaded conditions. We found that: 1) β1 and Cav3 colocalize in CM and coimmunoprecipitate from CM protein lysates; 2) β1 is detected in a subset of caveolae; 3) loss of Cav3 caused reduction of β1D integrin isoform and active β1 integrin from the buoyant domains in the heart; 4) increased expression of myocyte Cav3 correlates with increased active β1 integrin in adult CM; 5) in vivo pressure overload of the wild‐type heart results in increased activated integrin in buoyant membrane domains along with increased association between active integrin and Cav3; and 6) Cav3‐deficient myocytes have perturbed basal and stretch mediated signaling responses. Thus, Cav3 protein can modify integrin function and mechanotransduction in the CM and intact heart.—Israeli‐Rosenberg, S., Chen, C., Li, R., Deussen, D. N., Niesman, I. R., Okada, H., Patel, H. H., Roth, D. M., Ross, R. S. Caveolin modulates integrin function and mechanical activation in the cardiomyocyte. FASEB J . 29, 374‐384 (2015). www.fasebj.org